The wealth of genomic data has led to an explosion of computational and biological research endeavors directed at establishing the function of new genes. The proposed research will develop novel tools and methods for rapidly determining the function of orphan proteins. The data acquisition will employ a proprietary high-throughput assay that is capable of measuring the binding of a library of bioactive molecules to any protein, including proteins of unknown function. The data analysis will be accomplished using computational tools for intelligent data mining. The results will be useful both in characterizing unknown genes and in resolving ambiguities and errors in existing functional assignments. Phase I is divided into two segments: 1.) developing and refining screening and computational tools, and 2.) function determination for several unknown genes from Arabidopsis thaliana. The goal of Phase II will be to utilize these tools for high-throughput functional characterization of many unknown genes. PROPOSED COMMERCIAL APPLICATIONS: The technology developed in Phase I can be used to rapidly identify optimal disease targets for small-molecule therapeutics. The database of functional annotations created in Phase II, with associated analytical tools, will have significant market value as a pharmacogenomics resource.